Stereoselective Syntheses of 3’-Hydroxyamino- and 3’-Methoxyamino-2’,3’-Dideoxynucleosides

Aminonucleosides are used as key motifs in medicinal and bioconjugate chemistry; however, existing strategies toward 3′-hypernucleophilic amine systems do not readily deliver deoxyribo-configured products. We report diastereoselective syntheses of deoxyribo- and deoxyxylo-configured 3′-hydroxyamino- and 3′-methoxyamino-nucelosides from 3′-imine intermediates. The presence or absence of the 5′-hydroxyl-group protection dictates facial selectivity via inter- or intramolecular delivery of hydride from BH3 (borane). Protecting group screening gave one access to previously unknown 3′-methoxyamino-deoxyguanosine derivatives

Reactivities of electrophilic N–F fluorinating reagents

Electrophilic fluorination represents one of the most direct and useful methods available for the selective introduction of fluorine into organic compounds. Electrophilic fluorinating reagents of the N–F class have revolutionised the incorporation of fluorine atoms into both pharmaceutically- and agrochemically-important substrates. Since the earliest N–F reagents were commercialised in the 1990s, their reactivities have been investigated using qualitative and, more recently, quantitative methods. This review discusses the different experimental approaches employed to determine reactivities of N–F reagents, focussing on the kinetics studies reported in recent years. We make critical evaluations of the experimental approaches against each other, theoretical approaches, and their applicability towards practical problems. The opportunities for achieving more efficient synthetic electrophilic fluorination processes through kinetic understanding are highlighted

Graft copolymers of hydroxyethyl cellulose by a ‘grafting to’ method: 15N labelling as a powerful characterisation tool in ‘click’ polymer chemistry

We demonstrate how 15N labelling can be used to probe the success of ‘grafting to’ processes, through the preparation of well-defined graft copolymers of hydroxyethyl cellulose by combining RAFT polymerisation and copper-catalysed azide-alkyne cycloaddition (CuAAC). Using synthesised alkyne-functionalised chain transfer agents, short-chain (DP=10) poly(N-vinylpyrrolidone) (PVP) and poly(N-isopropyl acrylamide) (PNIPAAM) were prepared in high conversion in a controlled manner (ƉM of ~1.4 and 1.2 respectively). Separately, partially 15N-labelled N3-HEC was synthesised and characterised using solid state 13C, 15N CP-MAS NMR and FTIR spectroscopies. Alkyne-terminated PVP and PNIPAAM were grafted at different graft densities onto partially 15N-labelled N3-HEC using the click reaction. The hybrid HEC-g-polymer materials were fully characterised using solid state 13C and 15N CP-MAS NMR and FTIR spectroscopies. While 13C and FTIR spectroscopies gave indirect or weak evidence of CuAAC coupling, the cycloaddition of the alkyne-terminated polymers with N3-HEC was proven unambiguously by 15N solid state NMR spectroscopy. This indicates the utility of 15N labelling for probing the coupling efficiency of CuAAC reactions when employed in ‘grafting to’ processes with cellulosic substrates

Triazolium Salt Organocatalysis: Mechanistic Evaluation of Unusual Ortho-Substituent Effects on Deprotonation

Organocatalysis by N-heterocyclic carbenes is normally initiated by the deprotonation of precursor azolium ions to form active nucleophilic species. Substituent effects on deprotonation have an impact on catalytic efficiency and provide insight into general catalytic mechanisms by commonly used azolium systems. Using an NMR kinetic method for the analysis of C(3)-H/D exchange, we determined log kex–pD profiles for three ortho-substituted N-aryl triazolium salts, which enables a detailed analysis of ortho-substituent effects on deprotonation. This includes N-5-methoxypyrid-2-yl triazolium salt 7 and di-ortho-methoxy and di-ortho-isopropoxyphenyl triazolium salts 8 and 9, and we acquired additional kinetic data to supplement our previously published analysis of N-pyrid-2-yl triazolium salt 6. For 2-pyridyl triazoliums 6 and 7, novel acid catalysis of C(3)-H/D exchange is observed under acidic conditions. These kinetic data were supplemented by DFT analyses of the conformational preferences of 6 upon N-protonation. A C(3) deprotonation mechanism involving intramolecular general base deprotonation by the pyridyl nitrogen of the N(1)-deuterated dicationic triazolium salt is most consistent with the data. We also report kDO values (protofugalities) for deuteroxide-catalyzed exchange for 6–9. The protofugalities for 8 and 9 are the lowest values to date in the N-aryl triazolium series

The synthesis, conformation and hydrolytic stability of an N,S-bridging thiophosphoramidate analogue of thymidylyl-3 ',5 '-thymidine

A 3 ’ - N ,5 ’ - S -bridging thiophosphoramidate analogue of thymidylyl-3 ’ ,5 ’ -thymidine was synthesised underaqueous conditions.1H NMR conformational measurements show that the 3 ’ - N -substituted deoxyribosering is biased towards the ‘ north ’ , RNA-like conformation. Rate constants for hydrolysis of the analoguewere measured at 90 °C in the pH range 1.3 – 10.9. The pH-log k obs pro fi le displays a pH-independentregion between approximately pH 7 and 10 ( t 1/2 ∼ 13 days). Under acidic conditions, k obs displays a fi rstorder dependence on [H 3 O+]</p

A simple and efficient numerical scheme to integrate non-local potentials

As nuclear wave functions have to obey the Pauli principle, potentials issued from reaction theory or Hartree-Fock formalism using finite-range interactions contain a non-local part. Written in coordinate space representation, the Schrodinger equation becomes integro-differential, which is difficult to solve, contrary to the case of local potentials, where it is an ordinary differential equation. A simple and powerful method has been proposed several years ago, with the trivially equivalent potential method, where non-local potential is replaced by an equivalent local potential, which is state-dependent and has to be determined iteratively. Its main disadvantage, however, is the appearance of divergences in potentials if the wave functions have nodes, which is generally the case. We will show that divergences can be removed by a slight modification of the trivially equivalent potential method, leading to a very simple, stable and precise numerical technique to deal with non-local potentials. Examples will be provided with the calculation of the Hartree-Fock potential and associated wave functions of 16O using the finite-range N3LO realistic interaction.Comment: 8 pages, 2 figures, submitted to Eur. Phys. J.

The Work of the Course: validity and reliability in assessing English Literature

© 2017 National Association for the Teaching of English This article reflects on the values and practices of a revolutionary UK A level (senior secondary) course that achieved a high degree of validity and reliability in assessing the study of English literature. John Hodgson and Bill Greenwell were involved in its teaching and assessment from an early stage, and Greenwell's comments on an early draft of the article have been incorporated. The practice of literary response enshrined in the course was based on a striking application of “personal response” to literature, gave students opportunities to show capability in studying and writing a range of literary styles and genres, and engaged teachers regionally and nationally in a developed professional community of practice. It remains a touchstone of quality as well as of innovation in English curriculum and assessment

Come back Marshall, all is forgiven? : Complexity, evolution, mathematics and Marshallian exceptionalism

Marshall was the great synthesiser of neoclassical economics. Yet with his qualified assumption of self-interest, his emphasis on variation in economic evolution and his cautious attitude to the use of mathematics, Marshall differs fundamentally from other leading neoclassical contemporaries. Metaphors inspire more specific analogies and ontological assumptions, and Marshall used the guiding metaphor of Spencerian evolution. But unfortunately, the further development of a Marshallian evolutionary approach was undermined in part by theoretical problems within Spencer's theory. Yet some things can be salvaged from the Marshallian evolutionary vision. They may even be placed in a more viable Darwinian framework.Peer reviewedFinal Accepted Versio

Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters